Consuming Beetroot Juice Improves Slalom Performance and Reduces Muscle Soreness in Alpine Skiers under Hypoxic Conditions.

Background: Beetroot juice (BRJ) supplementation has been shown to increase sports performance under hypoxic conditions and to improve athletes' recovery. Objectives: In the present study, we aimed to investigate the effect of acute BRJ supplementation on slalom (SL) run performance and muscle soreness (MS) in Alpine skiers at moderate to high altitudes. Methods: Ten male Alpine skiers received 220 mL of BRJ (8.9 mmol/L nitrate) or placebo (PLA) in 2 sessions with a 7-d wash out interval in a randomized, crossover, PLA-controlled, double-blind study. The 90-s box jump (BJ90), agility hexagonal obstacle jump (Hex Jump), and wall-sit tests were measured before on-hill SL runs in both sessions. After the functional tests, SL run performance was measured by time to complete 2 runs on the SL course; immediately after each SL run, the rating of perceived exertion (RPE) was recorded. In addition, perceived MS was recorded using the visual analog scale at 12, 24, and 48 h after the SL runs. Results: The data were meticulously analyzed using 2-way repeated measures analysis of variance and paired t tests with significance set at P < 0.05. The findings were significant, indicating that compared with PLA, BRJ notably improved wall-sit and BJ90 performances (P < 0.05), while a substantial reduction was observed in RPE, Hex Jump, and MS (P < 0.05). A 1.74% shorter time to complete SL runs was observed in the BRJ group compared with the PLA group; however, there were no significant differences between the PLA and BRJ groups (P > 0.05). Conclusions: These results underscore the potential of BRJ supplementation to enhance sports performance and reduce MS in Alpine skiers under hypoxic conditions.

A Smart Ski Pole for Skiing Pattern Recognition and Quantification Application.

In cross-country skiing, ski poles play a crucial role in technique, propulsion, and overall performance. The kinematic parameters of ski poles can provide valuable information about the skier's technique, which is of great significance for coaches and athletes seeking to improve their skiing performance. In this work, a new smart ski pole is proposed, which combines the uniaxial load cell and the inertial measurement unit (IMU), aiming to provide comprehensive data measurement functions more easily and to play an auxiliary role in training. The ski pole can collect data directly related to skiing technical actions, such as the skier's pole force, pole angle, inertia data, etc., and the system's design, based on wireless transmission, makes the system more convenient to provide comprehensive data acquisition functions, in order to achieve a more simple and efficient use experience. In this experiment, the characteristic data obtained from the ski poles during the Double Poling of three skiers were extracted and the sample t-test was conducted. The results showed that the three skiers had significant differences in pole force, pole angle, and pole time. Spearman correlation analysis was used to analyze the sports data of the people with good performance, and the results showed that the pole force and speed (r = 0.71) and pole support angle (r = 0.76) were significantly correlated. In addition, this study adopted the commonly used inertial sensor data for action recognition, combined with the load cell data as the input of the ski technical action recognition algorithm, and the recognition accuracy of five kinds of cross-country skiing technical actions (Diagonal Stride (DS), Double Poling (DP), Kick Double Poling (KDP), Two-stroke Glide (G2) and Five-stroke Glide (G5)) reached 99.5%, and the accuracy was significantly improved compared with similar recognition systems. Therefore, the equipment is expected to be a valuable training tool for coaches and athletes, helping them to better understand and improve their ski maneuver technique.

Negative legacy effects of past forest use on native plant diversity in semi-natural grasslands on ski slopes.

Over the past century, grassland and forest ecosystems globally have been heavily influenced by land-use changes driven by diverse socioeconomic activities. Ski resorts are a modern land-use type associated with biodiversity loss in mountain ecosystems worldwide. Below the treeline, by contrast, some ski slopes have been shown to provide suboptimal semi-natural habitats for native grassland plants and animals, depending on specific construction and management practices. We compared environmental factors and grassland vegetation between two types of ski slopes in central Japan with different land-use histories: slopes constructed on old pastures (pasture slopes) and slopes constructed by clearing secondary forests or larch plantations established on abandoned pastures during the 1940s-1990s (forest slopes). We examined the effects of land-use history and machine grading as well as other environmental factors on ski slope vegetation, including total species richness and the richness of native, endangered, and exotic plants, using a total of 108 plots of 2 m × 10 m. Compared to pasture slopes, forest slopes exhibited significantly lower richness of native grassland species, including endangered species. Forest slopes were more graded than pasture slopes, resulting in lower native and higher exotic grassland species richness. A significantly lower duration of direct sunlight on forest slopes than on pasture slopes likely decreased endangered species richness. The lower species richness on forest slopes may be also caused by seed dispersal limitations. Our findings demonstrate that ski slopes have good potential to support numerous native grassland plant species, including endangered species, but this potential is significantly and negatively affected by forest use history and concomitant environmental changes. The conservation of semi-natural conditions on pasture slopes as habitats for native grassland species can be promoted through the maintenance of annual mowing practices, avoidance of machine grading, and wider ski courses.

Analgesic Effect of SKI306X on Chronic Postischemic Pain and Spinal Nerve Ligation-Induced Neuropathic Pain in Mice.

Neuropathic pain (NP) results from lesions or diseases affecting the peripheral or central somatosensory system. However, there are currently no drugs that are particularly effective in treating this condition. SKI306X is a blend of purified extracts of three oriental herbs (Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris) commonly used to treat osteoarthritis for their chondroprotective effects. Chronic postischemic pain (CPIP) and spinal nerve ligation (SNL) models were created by binding the upper left ankle of mice with an O-ring for 3 h and ligating the L5 spinal nerve, respectively. Mice with allodynia were injected intraperitoneally with 0.9% normal saline (NS group) or different doses (25, 50, or 100 mg/kg) of SKI306X (SKI groups). We assessed allodynia using von Frey filaments before injection and 30, 60, 90, 120, 180, and 240 min and 24 h after injection to confirm the antiallodynic effect of SKI306X. We also measured glial fibrillary acidic protein (GFAP) levels in the spinal cord and dorsal root ganglia to confirm the change of SKI306X administration. Both models exhibited significant mechanical allodynia. The intraperitoneal injection of SKI306X significantly increased the paw withdrawal threshold in a dose-dependent manner, as the paw withdrawal threshold was significantly increased after SKI306X administration compared with at baseline or after NS administration. GFAP levels in the SKI group decreased significantly (p < 0.05). Intraperitoneal administration of SKI306X dose-dependently attenuated mechanical allodynia and decreased GFAP levels, suggesting that GFAP is involved in the antiallodynic effect of SKI306X in mice with CPIP and SNL-induced NP.

Fatal injury of a skier during school training - case report.

The authors present the case of a fatal accident of a 16-year-old skier who crashed into a tree during a downhill skiing lesson at school. Although the skier was wearing a protective helmet at the time of the accident and his condition did not appear to be too serious immediately after the accident, he later died in hospital as a result of a craniocerebral injury with cerebral contusion and intracranial haemorrhage. His life could not be saved even by immediate neurosurgery, during which fragments of the broken protective helmet were removed from his cranial cavity. By analysing the international literature, the authors identify head and brain injuries as the most common immediate cause of death in downhill skiing and provide insights into the possibilities of preventing these injuries by simple technical means on the part of ski area operators. These means are in particular protective covers for lift columns and protective nets placed in front of fixed, non-movable obstacles on the track.

WDR61 ablation triggers R-loop accumulation and suppresses breast cancer progression.

Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen-induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony-forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R-loop, and loss of WDR61 leads to R-loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R-loop and counteracts endogenous DNA damage in tumor cells.

Performance and jump-to-jump development in the first female ski flying competition in history.

In 2023, for the first time in history, the international ski and snowboard federation (FIS) arranged an official ski flying competition where the 15 highest ranked women were allowed to participate. This study investigated jump-to-jump performance development in female ski flying, with men's results used as reference data. Official FIS data from all six jumps of women were evaluated together with the eight jumps by men. Performance was evaluated by a score, where the distance points compensated by wind were divided by take-off speed, enabling performance to be evaluated across jumps and sexes. Women improved performance by 96% from the first to the sixth jump, with two major leaps; from the first to the second jump and from the first to the second day. In contrast, men mainly improved from training to competition. The best women had performance scores equivalent to the 10-20 best ranked men and the sex-difference between the top 3 athletes was 26.2%. This difference was thereafter compared to similar results in the normal and large hill World championship in Planica 2023, in which sex-differences between the top 3 were 8.6% and 14.6% in normal and large hill. This historical competition showed the importance of gaining practical experience with ski flying on performance, exemplified by the large improvement of female athletes. This, together with the enlarge sex-differences in large compared to normal hills, indicates that female ski jumpers have a particularly large improvement-potential in ski flying and must gain specific experience on this through traning and competitions.

Investigation of the effects of an 8-week cross-country skiing exercise program on various reaction time parameters, selective attention and academic achievement in adolescents.

Exercise slows or helps reverse the shrinkage of key cognitive brain regions such as the hippocampus, which is important for information processing, learning, reasoning and planning. For this reason, it is thought that regular exercise of individuals, especially during adolescence, which is considered one of the most important processes of development, can increase their performance in areas where cognitive activities are at the forefront. Cross-country skiing, one of the leading branches of winter sports, has a much more complex structure, unlike the branches that are widely preferred today (football, basketball, volleyball, etc.) and is a branch where many motor skills are exhibited at the same time For this reason, the effect of cross-country skiing, which is defined as more complex and difficult in terms of biomotor than other branches, on cognitive activities is a matter of curiosity. Therefore, the aim of the research is; to examine the cognitive effects of cross-country skiing exercise. The study involved 54 (26 male, 28 female) adolescents who had no prior experience in any licensed sports. The average age of the participants was determined as 12.61 ± 1.32. The participants were divided in experimental and control groups. Reaction performances were determined using the ÇAGIN Hand and Foot Reaction Tests, selective attention performances were evaluated using the Flanker Test and academic achievement was determined using the e-Okul system. Two-way ANOVA revealed significant group × time interactions for hand and foot simple, selective, discriminative reaction time, selective attention and academic achievement (p < 0.05) due to improved values at post-test for the experimental group but not for the control groups. No significant group × time interactions were observed for correct reaction rate for all reaction parameters (p > 0.05). The study concludes that the cross-country skiing exercise, which was applied to adolescents for eight weeks, had a positive impact on the parameters of reaction, selective attention and academic achievement. Therefore, parents are suggested to encourage their children to exercise and engage in sports practices like cross-country skiing to improve cognitive and academic performance during adolescence.

Combination of high anti-SKI and low anti-TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma.

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s-SKI-Abs and s-TMED5-Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s-SKI-Ab-positive and s-TMED5-Ab-negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s-SKI-Ab-positive and s-TMED5-Ab-negative cases showed an even clearer difference in overall survival as compared with that of s-SKI-Ab-negative and s-TMED5-Ab-positive cases. The s-SKI-Ab and s-TMED5-Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.

Changes in roller skiing economy among Nordic combined athletes leading up to the competition season.

The purpose of this study was to compare roller skiing economy during different training phases in Nordic combined (NC) athletes and determine the aerobic and anaerobic factors responsible for changes in skiing economy. Seven elite NC athletes underwent incremental load tests on a large buried treadmill in both spring and autumn using roller skis. Measurements included oxygen uptake, respiratory exchange ratio, and blood lactate concentration. Roller skiing economy was calculated from aerobic and anaerobic energy system contributions, and overall roller skiing economy was determined by combining the two. Comparisons were made between the skiing economies obtained in the two measurement sessions. Physical characteristics and incremental test performance remained consistent between the two measurement sessions. The overall skiing economy at each speed significantly improved toward the competition season (p < 0.05). Similarly, the contribution of anaerobic energy system at each speed showed significant improvement (p < 0.05). In contrast, the contribution of aerobic energy system did not change between the two measurement sessions. This study reveals that NC athletes enhance their skiing economy at the same speed during submaximal efforts in preparation for the competition season. This improvement is predominantly associated with an improvement in the contribution of anaerobic energy system.

Distributed IMU Sensors for In-Field Dynamic Measurements on an Alpine Ski.

Modern ski design is an inherently time-consuming process that involves an iterative feedback loop comprised of design, manufacturing and in-field qualitative evaluations. Additionally consumers can only rely on qualitative evaluation for selecting the ideal ski, and due to the variation in skier styles and ability levels, consumers can find it to be an inconsistent and expensive experience. We propose supplementing the design and evaluation process with data from in-field prototype testing, using a modular sensor array that can be ported to nearly any ski. This paper discusses a new distributed Inertial Measurement Unit (IMU) suite, including details regarding the design and operation, sensor validation experiments, and outdoor in-field testing results. Data are collected from a set of spatially distributed IMUs located on the upper surface of the ski. We demonstrate that this system and associated post-processing algorithms provide accurate data at a high rate (>700 Hz), enabling the measurement of both structural and rigid ski characteristics, and are robust to repetitive testing in outdoor winter conditions.

Bilateral Dorsal Nail Curvature of the Thumb Distal Phalanx - A Case Report.

Congenital dorsal curvature of the distal phalanx has been previously described as 'reverse Kirner' or 'ski-jump' deformity. This report describes bilateral occurrence in the thumbs. A 13-year-old male presented with difficulty caring for his thumbnails and in picking up small objects. Examination showed dorsal curvature of the distal phalanges of both thumbs, with greater curvature of the right side. Radiographs showed wedge-shaped epiphyses and dorsal curvature without coronal plane deviation of the distal phalanges. There was objective and subjective decrease in function associated with lateral pinch and tripod grasp. The reported aetiopathogenesis for Kirner deformity cannot explain the observed dorsal curvature. The bilateral nature makes a secondary physeal cause unlikely and suggests an embryologic basis. Due to the noticeable deficits in function, operative intervention may be warranted. Level of Evidence: Level V (Therapeutic).

Ski ameliorates synovial cell inflammation in monosodium iodoacetate-induced knee osteoarthritis.

Knee osteoarthritis (KOA) is one of the most common degenerative diseases and is characterized by cartilage degeneration, synovial inflammation, joint stiffness and even loss of motor function. In the clinical treatment of arthritis, conventional analgesic and anti-inflammatory drugs have great side effects. We have evaluated the possibility of the endogenous transcription regulator Ski as an anti-inflammatory alternative in OA through experimental studies in animal models and in vivo and in vitro. Male Sprague‒Dawley rats were injected with monosodium iodoacetate (MIA) into the knee joints to induce symptoms identical to those of human OA. We isolated knee synovial tissue under sterile conditions and cultured primary synovial cells. In vitro, Ski inhibits the proinflammatory factors IL-1ß, IL-6 and TNF-α mRNA and protein expression in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLSs) and U-937 cells. In addition, Ski attenuates or inhibits OA-induced synovial inflammation by upregulating the protein expression of the anti-inflammatory factor IL-4 and downregulating the protein expression of downstream molecules related to the NF-κB inflammatory signaling pathway. In vivo, Ski downregulated proinflammatory factors and p-NF-κB p65 in KOA synovial tissue and alleviated pain-related behaviors in KOA rats. These experimental data show that Ski has strong anti-inflammatory activity. Ski is an endogenous factor, and if used in the clinical treatment of OA, the side effects are small. However, the anti-inflammatory mechanism of Ski must be further studied.

Anterior cruciate ligament injuries in elite ski jumping reliably allow return to competition but severely affect future top performance.

PURPOSE: In recent years, anterior cruciate ligament (ACL) injuries have been frequently observed in ski jumping. However, available data in this discipline are very scarce. Therefore, the purpose of this study was to investigate whether an ACL injury in elite-level ski jumping limits the performance level after ACL reconstruction (ACLR). METHODS: Both male and female elite-level ski jumpers from five national A-teams who suffered an ACL injury were identified retrospectively by searching available media reports and Fédération Internationale de Ski (FIS) database. World Cup (WC) results and time-out-of-competition before ACL injury and after ACLR were compared. Only athletes who suffered the injury during or after the 2009-2010 season and who participated in at least one WC competition before the injury were included in this study. The level of athletes' performance from two full seasons before until three seasons after the injury was compared. RESULTS: Eighteen elite-level ski jumpers (11 males/seven females) were eligible for the study. All male and four female athletes returned to professional competition after ACLR. One female athlete ended her career due to prolonged recovery and two have not yet recovered due to a recent injury. The mean return-to-competition (RTC) time was 14.6 months in males and 13.5 months in females. The mean WC placement decreased after the ACL injury: two seasons before injury the mean position was 17.9 ± 11.0 (n = 12), one season before it was 22.4 ± 12.8 (n = 15). After recovery, the mean placement in seasons 1-3 was: 26.4 ± 8.9 (n = 7), 25.7 ± 10.3 (n = 13), 33.6 ± 12.2 (n = 10) (p = 0.008). Among the athletes returning to competition, only six males and three females reached their preinjury level and only one male and one female (compared to seven males and three females preinjury) reached an individual top-3 placement after ACLR, accounting for less than 10% of podiums compared to preinjury. CONCLUSION: Only 60% of the professional ski jumpers reached the preinjury level and less than 15% reached a top-3 placement after the ACL injury. These results support the fact that ACL tear during a ski jumping career may be a significant factor limiting high-level performance. In terms of clinical relevance, the findings implicate the need to analyse the reasons of these very low rates of return to elite-level performance, to analyse ACL injury and RTC rates at lower levels of performance and to develop specific prevention strategies in order to reduce the number of ACL injuries in this sport. LEVEL OF EVIDENCE: Level IV.

TDG generation in a ski-jump spillway with a fully or partial-flip bucket.

Ski-jump spillways are frequently used as discharge structures for high dams during floods with high energy heads. The selection of bucket types at the end of spillways has a pronounced effect on the hydraulics of jet characteristics, such as trajectories and entrained air features. However, there is no literature reporting how changes in the bucket types influence TDG generation. This study compares the hydraulic characteristics and TDG mass transfer properties of a hydraulic project under construction using both the traditional fully-flip bucket and the partial-flip bucket configurations. The results indicate that, the use of the partial-flip bucket at the end of the spillway significantly disperses the water flow and yields better energy dissipation effects. At low flow rates (lower than 400 m3/s for the dam in this study), there is little difference in the downstream TDG saturation between the traditional fully-flip bucket and the partial-flip bucket, the average difference is 1.6 % in three cases with a low flow rate. However, at high flow rates (higher than 400 m3/s), the partial-flip bucket generates more TDG compared to the traditional fully-flip bucket, reaching up to 6.2 % at the maximum flow rate. This phenomenon stems from significant changes in the hydrodynamics of the stilling basin at high flow rates due to variations in the flip bucket type. When strict control of TDG generation is necessary downstream of dams, the use of the partial-flip bucket should be carefully considered. This is because, at high flow rates, the partial-flip bucket might result in higher TDG saturation than the fully-flip bucket.

Patient-reported hip pain and function are worse among elite Nordic ski athletes competing in ski jumping versus Nordic combined: a cross-sectional analysis.

OBJECTIVES: Nordic ski athletes are at increased risk of developing hip pain and dysfunction secondary to femoroacetabular impingement syndrome (FAIS), but it is unclear whether hip symptomatology differs between ski jumping (SJ) and Nordic combined (NC) athletes. The purpose of this study was to compare patient-reported hip pain and dysfunction between elite Nordic ski athletes participating in SJ versus NC. METHODS: A cross-sectional study was conducted involving SJ and NC athletes who competed at the international and U.S. national levels during the 2021-2022 season. Subjects were excluded if they had hip surgery within two years prior to enrollment. Subjects were asked to undergo diagnostic workups for FAIS, including physical examination and plain radiographic imaging. Subjects were asked to complete a survey that collected information on athletic and training history and to complete the hip disability and osteoarthritis outcome score (HOOS). Demographics, athletic/training history, and HOOS sub-scores were compared between the SJ and NC groups using the Student's t-test, Wilcoxon rank-sum test, or Fisher's exact test, as appropriate. p-values < 0.05 were considered significant. RESULTS: Twenty-four athletes (13 SJ, 11 NC) were included in the study. There were no statistically significant differences in age, sex, BMI, or age of menarche between the two groups (all p â€‹> â€‹0.05). There were also no statistically significant differences in the number of prior sports participated in, total hours of participation in prior sports, or total hours of training in Nordic specialization (all p â€‹> â€‹0.05). Among the 18 athletes who underwent physical examination (9 SJ, 9 NC), there were no statistically significant inter-group differences in hip range of motion or incidence of positive impingement tests (all p â€‹> â€‹0.05). Among the 19 athletes who underwent imaging (9 SJ, 10 NC), there were no statistically significant inter-group differences in the incidence of cam or pincer morphology in at least one hip (all p â€‹> â€‹0.05). SJ athletes had statistically significantly worse HOOS sub-scores for hip symptoms and stiffness, hip function in sports/recreational activities, and hip-related quality of life compared to NC athletes (all p â€‹< â€‹0.05). CONCLUSION: Elite SJ athletes have worse self-reported hip function compared to elite NC athletes, despite comparable demographics, athletic history, and duration of ski training. LEVEL OF EVIDENCE: IV.

Respiratory Exposure to Highly Fluorinated Chemicals via Application of Ski Wax and Related Health Effects.

PURPOSE: Waxes containing per- and polyfluoroalkyl substances (PFAS) are applied to the base of skis and snowboards ("skis") to reduce friction with the snow surface and improve glide. PFAS exposure can adversely impact cardiometabolic, thyroid, liver, kidney, reproductive, and immune health and are associated with increased risk of certain cancers. In the present review, we summarize the state of the science on PFAS exposure from fluorinated ski wax use, including acute respiratory health effects and PFAS concentrations in biological and environmental media collected from ski waxing settings. RECENT FINDINGS: Perfluoroalkyl carboxylic acid (PFCA) concentrations in serum and air collected from professional wax technicians and the rooms where waxes are applied are among the highest of any occupation investigated to date, including the fluorochemical industry. High airborne concentrations of fluorotelomer alcohols contribute to high body burdens of certain PFCAs among ski waxers. Fluorinated ski waxes are a significant source of PFAS exposure for people waxing skis and/or spending time in areas where waxing occurs. We highlight recommendations for future research, policy, and technologies needed to address PFAS exposures from fluorinated wax use.

We know a lot about little and little about a lot: A contextualized scoping review on injury prevention in alpine ski racing.

BACKGROUND: Our goal was to summarize and contextualize the available literature on alpine ski racing injury epidemiology, injury etiology, injury prevention measures, injury prevention context, and implementation issues. MATERIALS AND METHODS: We searched four electronic databases using predetermined search terms. We included original studies that assessed injury, injury risk factors, and injury mechanisms, and assessed and reported the effect of an injury prevention measure in alpine ski racing. Two authors independently conducted title-abstract screening, and one performed the full-text review. For data synthesis and categorization, we used the Translating Research into the Injury Prevention Practice framework and a modified and adapted version of the Haddon matrix. RESULTS: Of the 157 included studies, most corresponded to injury epidemiology and etiology, whereas few studies encompassed injury prevention measure development, implementation and evaluation. Preventive interventions targeting equipment, rules and regulations, course design and snow preparation were the most prevalent in the literature. Furthermore, various contextual factors in the current literature have been found, including gender, competition level, countries and federations, and time periods within a season. CONCLUSIONS: We provided an in-depth and comprehensive overview of the current state-of-the-art in the alpine ski racing context. We know a lot about little and little about a lot across all the areas associated with injury prevention in such context. The limitations in the literature yield a road map for designing future injury prevention studies to address the key gaps identified. A more comprehensive context-driven approach throughout all stages of injury prevention would benefit the ultimate implementation of effective preventive strategies.

SKI-349, a Sphingosine Kinases 1/2 Inhibitor, Suppresses Cell Viability, Invasion, and AKT/mTOR Signaling Pathway, and Shows Synergistic Cytotoxic Effects with Sorafenib in Hepatocellular Carcinoma.

SKI-349 is a novel sphingosine kinases (SPHK) inhibitor with anti-tumor effects. This study aimed to assess the effect of SKI-349 on cell biological behaviors, downstream pathways, and its synergistic effect with sorafenib in hepatocellular carcinoma (HCC). HCC cell lines (Huh7 and Hep3B) were treated with SKI-349 at concentrations of 1, 2, 4, or 8 µM. Then, SPHK1/2 activity, cell viability, proliferation, apoptosis, invasion, and protein expressions of phosphorylated-protein kinase B (p-AKT), AKT, phosphorylated-mammalian target of rapamycin (p-mTOR) and mTOR were detected. Combination index values of SKI-349 (0, 1, 2, 4, or 8 µM) and sorafenib (0, 2.5, 5, 10, or 20 µM) were calculated. SKI-349 decreased the relative SPHK1 and SPHK2 activity compared with blank control in a dose-dependent manner in the Huh7 and Hep3B cell lines. Meanwhile, SKI-349 reduced cell viability, 5-ethynyl-2'-deoxyuridine (EdU) positive cells, and invasive cells, while it increased apoptotic cells compared to blank control in a dose-dependent manner in Huh7 and Hep3B cell lines. Based on the western blot assay, SKI-349 decreased the ratio of p-AKT to AKT and that of p-mTOR to mTOR compared with blank control in a dose-dependent manner in the Huh7 and Hep3B cell lines. Additionally, SKI-349 combined with sorafenib declined cell viability with concentration gradient effects compared to SKI-349 sole treatment, and they had synergistic cytotoxic effects in Huh7 and Hep3B cell lines. SKI-349 suppresses SPHK1 and SPHK2 activity, cell viability, invasion, and AKT/mTOR signaling pathway, as well as exhibits a synergistic cytotoxic effect with sorafenib in HCC.

Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses.

The emerging viruses SARS-CoV-2 and arenaviruses cause severe respiratory and hemorrhagic diseases, respectively. The production of infectious particles of both viruses and virus spread in tissues requires cleavage of surface glycoproteins (GPs) by host proprotein convertases (PCs). SARS-CoV-2 and arenaviruses rely on GP cleavage by PCs furin and subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P), respectively. We report improved luciferase-based reporter cell lines, named luminescent inducible proprotein convertase reporter cells that we employ to monitor PC activity in its authentic subcellular compartment. Using these sensor lines we screened a small compound library in high-throughput manner. We identified 23 FDA-approved small molecules, among them monensin which displayed broad activity against furin and SKI-1/S1P. Monensin inhibited arenaviruses and SARS-CoV-2 in a dose-dependent manner. We observed a strong reduction in infectious particle release upon monensin treatment with little effect on released genome copies. This was reflected by inhibition of SARS-CoV-2 spike processing suggesting the release of immature particles. In a proof of concept experiment using human precision cut lung slices, monensin potently inhibited SARS-CoV-2 infection, evidenced by reduced infectious particle release. We propose that our PC sensor pipeline is a suitable tool to identify broad-spectrum antivirals with therapeutic potential to combat current and future emerging viruses.